Noncovalent interactions between molecules play an important role in determining the structures and properties of molecular assemblies in biology and chemistry. An increasing number of studies have reported evidence for CH-Y (Y = N, O, F) and XH-pi (X = N, O, S) hydrogen bonds. Accordingly, investigations aimed at an energetic quantification of individual interactions with such H-bonds are of paramount importance for improved drug design and lead optimization. The aim of this project is to provide quantitative information about these interactions with carefully designed molecular devices. Specifically, this proposal includes the design, synthesis, VT NMR study, and theoretical calculations of model compounds capable of revealing the strength of a CH-Y (Y = N, O) and an XH-pi (X = N, O, S) hydrogen bonds. Several series of heterocyclic and extended triptycene derivatives and amide-based models have been designed and are planned to be synthesized in the laboratory. These compounds contain a bond that rotates slowly enough to allow direct NMR observation of two rotamer populations, but is rapid enough for equilibration. Thermodynamic parameters can then be determined by measuring the equilibrium constants at various temperatures. The influence of molecular structure on these weak interactions will be studied by substituent variations. In summary, a new model and a new section on XH-pi (X = N, O, S) interactions have been added based on our preliminary results. The experimental results will be used in conjunction with the computational study to evaluate the magnitude of weak H-bonds in solution. With a better knowledge of the magnitude of the weak interactions, a better understanding of the contributions from these interactions in molecular recognition involving biological macromolecular systems and in Lewis acid catalysts can be achieved. The understanding of these weak interactions is essential for rational drug design and lead optimization. [unreadable] [unreadable]